Orexins (hypocretins) directly excite tuberomammillary neurons

Autor: L, Bayer, E, Eggermann, M, Serafin, B, Saint-Mleux, D, Machard, B, Jones, M, Mühlethaler
Jazyk: angličtina
Rok vydání: 2001
Předmět:
Hypothalamic Area
Lateral/cytology/ drug effects/metabolism

Action Potentials
Biotin
Efferent Pathways
Synaptic Transmission
Organ Culture Techniques
mental disorders
Animals
Biotin/ analogs & derivatives/diagnostic use
Carrier Proteins/metabolism/ pharmacology
Narcolepsy/metabolism/pathology/physiopathology
Wakefulness
Synapses/drug effects/metabolism
Efferent Pathways/cytology/drug effects/metabolism
Narcolepsy
Neurons
Orexins
Neurons/cytology/ drug effects/metabolism
Neuropeptides
digestive
oral
and skin physiology

Intracellular Signaling Peptides and Proteins
Wakefulness/ drug effects/physiology
Neuropeptides/metabolism/ pharmacology
ddc:616.8
Histamine/ metabolism
Rats
nervous system
Molecular Probes/diagnostic use
Hypothalamic Area
Lateral

Molecular Probes
Synapses
Synaptic Transmission/drug effects/physiology
Action Potentials/ drug effects/physiology
Carrier Proteins
psychological phenomena and processes
Histamine
Zdroj: European Journal of Neuroscience, Vol. 14, No 9 (2001) pp. 1571-1575
ISSN: 0953-816X
Popis: Wakefulness has recently been shown to depend upon the newly identified orexin (or hypocretin) neuropeptides by the findings that alteration in their precursor protein, their receptors or the neurons that produce them leads to the sleep disorder narcolepsy in both animals and humans. The questions of how and where these brain peptides act to maintain wakefulness remain unresolved. The purpose of the present study was to determine whether the orexins could directly affect hypothalamic histaminergic neurons, which are known to contribute to the state of wakefulness by their diffuse projections through the brain. Using brain slices, we recorded in the ventral tuberomammillary nuclei from neurons identified as histaminergic on the basis of their previously described morphological and electrophysiological characteristics and found that they were depolarized and excited by the orexins through a direct postsynaptic action. We then compared the depolarizing effect of orexin A and B and found that they were equally effective upon these cells. This latter finding suggests that the effect of orexins is mediated by orexin type 2 receptors, which are those lacking in narcoleptic dogs. Our results therefore show that the histaminergic neurons of the tuberomammillary nuclei represent an important target for the orexin system in the maintenance of wakefulness.
Databáze: OpenAIRE